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Researchers Develop
Effective Mastitis Treatments

It could be argued that one word should
strike fear in the minds of serious connoisseurs of milk, cheese, yogurt,
butter, ice cream and other dairy products: mastitis. That's because mastitis,
an udder inflamation caused by bacterial infection, leads to lower milk
production, wasted milk and a shorter life for infected dairy cows. It's the
single most costly dairy cow disease.

Actually, American consumers have nothing
to worry about. The United States' dairy production was 169.8 billion pounds in
2002, an increase of 2.6 percent from the previous year. But mastitis is still
bad news for cows and dairy producers.

Bacteria invading a cow's mammary gland
absorb milk nutrients while secreting poisonous endotoxins that destroy mammary
tissue. If these toxins escape the gland and spread throughout the cow's body,
they eventually cause organ failure and death.

Annual losses due to mastitis are
estimated at more than $2 billion in the United States, and about 3 million
dairy cows each year show visible signs of acute infection. Of those 3 million,
about 300,000 die from shock induced by the endotoxin or have to be culled.
Antibiotics help, but resistant pathogens can make them ineffective. Milk
containing antibiotics is not allowed to be sold to consumers, so producers
have to wait a few days before selling milk from treated cows.

Mastitis causes an additional $400
million loss to the beef industry, and affects goats, sheep and pigs. The
impact in the latter species has not been fully evaluated, particularly as it
affects their continued use for breeding and the survival rate of their newborn
offspring.

Now for the good news: Veterinarians could soon have an
effective way to treat and prevent acute endotoxin shock in dairy cows for the
first time, thanks to ARS scientists in Beltsville, MD.

Max Paape, a dairy scientist with ARS'
Immunology
and Disease Resistance Laboratory (IDRL), and colleagues have applied for a
patent on the cloned gene that codes for
a protein
called CD14 naturally suspended in cow's milk and blood plasma, its
recombinants, and its application for treating mastitis-infected cows and
preventing future cases.

Paape, fellow IDRL scientist Dante
Zarlenga and graduate student Yan Wang discovered the protein in cow milk in
1994-95. They knew it was the soluble form of CD14 that increases during
coliform infections in humans and laboratory animals. Soluble CD14 is formed
when membrane-bound CD14 is shed from the surface of some white blood cells.
Coliform bacteria, found throughout dairy barns, account for about 40 to 50
percent of all cases of dairy mastitis in the United States.

CD14 binds and neutralizes endotoxins.
When CD14 is injected into the mammary gland during an infection, one end hooks
up with a pathogen's endotoxin and the other snags a mammary cell from the
cow's mammary system. Then the CD14 complex causes the mammary cell to secrete
chemicals that attract specialized white blood cells, called neutrophils, to
the infection site to destroy the coliform pathogens. CD14 protects cows from
shock and reduces clinical symptoms associated with coliform mastitis. In
studies, it was 100 percent effective in preventing mastitis caused by
Escherichia coli in lactating dairy cows.

Paape developed procedures to count
cells, such as neutrophils, that are present in milk to fight infections, and
he coined the term "milk somatic cells" to describe them. Somatic cell counts
(SCC) are now used to determine the price dairy farmers receive for milk; the
lower the SCC, the better the price. The procedure is used to diagnose infected
cows and is an index of milk quality around the world.

Work with CD14 is cutting-edge technology
that's also being used in research with humans to increase the killing power of
immune cells.

CD14 also sensitizes the lining of a
cow's mammary gland to very low levels of endotoxin, which is produced by just
a few types of bacteria called gram-negative bacteria. Once the mammary cells
are sensitized, they start an attack early enough to prevent the cow from
getting sick.

The cloned gene for CD14 can be designed
and inserted into a cow's mammary gland so it will secrete the protein only in
milk. Paape and colleagues are working on a delivery system for the CD14
protein. They are seeking commercial business partners to license the
technology and produce CD14.

Paape and Jai-Wei Lee and Xin Zhao,
collaborators at McGill University in Canada, are also interested in the
natural causes that lead to an increase of CD14 in cow's milk. They are
studying how CD14 concentration is affected by different stages of lactation,
somatic cell count, the presence of bacteria and the level of endotoxin
secreted by gram-negative bacteria that bind to CD14 receptors.

Transgenic mice expressing recombinant
CD14 from cows are being produced by ARS scientist Bob Wall. They will be
challenged with E. coli to see if the CD14 prevents mastitis.
Eventually, bioengineered cows could be developed with immunity to
mastitis.

Another 30 to 40 percent of all clinical
dairy mastitis cases are caused by Staphylococcus aureus infections. A
retired colleague of Paape's, A. J. Guidry, was part of a team that developed a
vaccine to immunize heifers to prevent mastitis caused by all strains of S.
aureus. The vaccine was 100 percent effective in protecting heifers from
that gram-positive bacterium. The vaccine would prevent mastitis at the very
beginning of a cow's productive life. When the vaccine was used with
antibiotics, it was 70 percent effective in curing chronic mastitis infections.
Testing is under way for both applications in commercial herds around the
United States. ARS has applied for a patent and the agency is seeking licensees
to produce and market the vaccine.

Research Briefs

ARS researchers developed an
oil emulsion
vaccine of inactivated Salmonella enteritidis, protecting hens exposed to
the organism. A patent application has been filed and the vaccine is available
for licensing. Peter Holt
(706) 546-3442

A new software program
developed by ARS scientists and cooperators estimates the relative economic
value of multiple traits in beef cattle, instead of just one specific trait in
each type. This allows producers to rank cattle based on the their potential to
produce the most profitable offspring. Michael D. MacNeil (406)
232-8213

A hormone-producing gene that may
suppress appetite in
chickens is being sequenced to find out why broiler birds tend to overeat
when given free access to feed. ARS scientists are comparing egg-laying
chickens with broilers to see which genetic components govern the differences
in feed intake and calorie expenditure in each type. Mark Richards (301)
504-8892

Ovulation-inducing techniques that cause cows to
have medium-sized follicles at the time of artificial insemination could ensure
high pregnancy
rates, according to ARS scientists and university collaborators. The
procedure also eliminates the need to detect when cows go into heat. Thomas W. Geary (406) 232-8215

A new, natural-based algicide is being tested to
see if it's safer than current treatments used in catfish ponds to
prevent
off-flavors. ARS has filed a patent application on the algicide derived
from a compound found in ryegrass. Kevin Schrader (662) 915-1144

ARS researchers and collaborators are
sequencing the
chromosomes of bacteria that cause Johne's disease and bovine brucellosis
as well as the bacterium that causes leptospirosis. They hope the sequencing
could lead to new tests and vaccines for these cattle diseases. David P. Alt (515) 663-7645

Fish oil containing omega-3 fatty acids
helped develop the
immune systems of young, weaned pigs. After both groups were challenged
with an endotoxin, ARS and university collaborators found that pigs given feed
with fish oil ate more and were better prepared to fight the toxin than those
given a control diet. Jeff Carroll
(573) 882-6261